The overarching purpose of this project is to further our understanding of the neural circuitry underlying the regulation of negative affect, with a focus on prefrontal cortex (PFC), anterior cingulate cortex (ACC) and amygdala. Variations in affective style are assumed to be based in large part on variations in the capacity or skill to regulate emotion. A series of functional magnetic resonance imaging (fMRI) studies are proposed to examine basic neural mechanisms of voluntary emotion regulation in response to both emotional picture viewing as well as to a paradigm that elicits anticipatory anxiety. Individual differences in the functional neuroanatomical substrates of emotion regulation will be examined and relations with electrophysiological measures of prefrontal activation asymmetry and with startle probe measures of emotion regulation will be determined. We will also examine the extent to which regulatory skill evidenced in response to phasic stimuli in an acute laboratory paradigm are related to regulation of cortisol in response to the Trier Social Stress Test administered on two occasions. Finally two experiments with samples derived from Project V (adolescents are varying risk for internalizing disorders) and Project IV (MZ and DZ 7-9 year old twin pairs) will be conducted. One of these studies will utilize the same emotion regulation to determine whether adolescents selected to be at risk for internalizing disorders differ in their patterns of PFC, ACC and amygdala activation and other study will continue our psychophysiological analysis of temperament in MZ and DZ twins. The experiments in this project will collectively advance our knowledge of the neural basis and physiological concomitants of affective styles that are associated with vulnerability to psychopathology and will facilitate the early detection of risk for mood and anxiety disorders.